Skeletal Muscle Relaxants Dr Naser Ashraf

Types of skeletal muscle relaxants: 2 groups Neuromuscular blockers Relax normal muscles (surgery and assistance of ventilation) No central nervous system activity. Used primarily as a part of general anesthesia Spasmolytics Reduce spasticity Centrally acting (except dantrolene which act on the skeletal muscle) Used in a variety of neurologic conditions

Skeletal Muscle Relaxants Centrally acting Neuromuscular blockers Directly acting Spasmolytics Non-depolarizing Depolarizing (Competitive) D tubocurarine Pancuronium Vecuronium Atracurium Mivacurium (Non-Competitive) Succinylcholine Decamethomium Diazepam Chlorzoxazone Tizanidine Baclofen Dantrolene

Skeletal Muscle contraction Action Potential Ca 2+ Motor neuron Na + ACH          Na + Skeletal Muscle ACHEsterase N M receptor

Mechanism of action of Neuromuscular Blockers

Ach A SCh Contraction Relaxation Flaccid Paralysis Ch Depolarization No Depolarization Persistent Depolarization SCh No contraction Contraction Relaxation ( Fasciculation) Normald-TubocurarineSuccinylcholine Repolarization

Competitive Antagonists (Non-depolarizing Blockers)

(Non-depolarizing blockers) Long-acting: d tubocurarine, pancuronium Intermediate: Atracurium, vecuronium, rocuronium, Short-acting: Mivacurium

Mechanism of Action Competitive Antagonism Ach Agonist d-Tubocurarine Antagonist Motor End Plate Anti-cholinestrases (neostigmine, edrophonium) which preserve acetylcholine are used to reverse the effect of d-tubocurarine Affinity : Yes Intrinsic action : No N M receptor

Actions Muscle weakness  Flaccid paralysis Order of muscle affected: –Extrinsic eye muscles, muscles of finger –Neck muscles (muscles of phonation and swallowing) –Face –Hands, –Feet –Trunk –Respiratory muscles (intercostal and diaphragm) Recovery in the reverse order Consciousness, appreciation of pain not affected

Actions Autonomic ganglion blocking property Histamine release (by d-tubocurarine) CVS –Significant fall in BP –Increase in Heart rate –Vagal gangionic blockade (also ‘ve’ and ‘pan’) Newer competitive blockers: –Negligible effect on BP and HR

Adverse effects Hypotension Tachycardia Respiratory paralysis Bronchospasm Aspiration of gastric contents

Advantages of synthetic (Newer) competitive blockers Less histamine release Do not block autonomic ganglia Spontaneous recovery with most of drugs Rapacuronium & rocuronium have rapid onset Atracuronium: Hoffmans elimination Mivacurium short acting

Uses As an adjunct to general anaesthesia –For producing satisfactory skeletal muscle relaxation For facilitating endotracheal intubation –Rocuronium preferred due to rapid onset of action –Succinylcholine is better due to short lasting duration

Depolarizing Blocker (Non-competitive Antagonist) Succinylcholine One Drug, Two blocks, Brief and quick, Genetic variability in metabolism, Malignant hyperthermia

Succinyl Choline Acetylcholine Two molecules of Acetylcholine) Depolarising muscle relaxants Skeletal Muscle Relaxants Quaternary ammonium Quaternary ammonium

Mechanism of action Agonist at Nicotinic (N M ) receptor Produces neuromuscular block by overstimulation, end plate is unable to respond to further stimulation. Longer lasting or persistent depolarization

Actions Small rapidly moving muscles (eye, jaw, larynx) relax before those of limbs and trunks Ultimately intercostals and finally diaphragm paralysis occur  respiratory paralysis Recovery in the reverse order Muscle relaxation: Onset: within 1 min; peak: 2 min, duration: 5 min; longer duration relaxation requires continued IV infusion Succinylcholine

Uses Suitable for short-term procedures Rapid endotracheal intubation during induction of anaesthesia During Electro-Convulsive shock Therapy (ECT) –To prevent injury Succinylcholine

Adverse Effects Transient  Intraocular Tension Hyperkalemia : Fasciculations release potassium in blood Succinylcholine apnoea Malignant hyperthermia: when used alng with halothane in general anaesthesia –Treatment is by rapid cooling of patient & dantrolene i.v Muscle pain Succinylcholine

Treatment of succinylcholine apnoea No antidote is available Fresh frozen plasma should be infused Patient should be ventilated artificially untill full recovery

Comparison of Competitive and Depolarizing Blocking Agents Sr.noCompetitiveSuccinyl choline 1Competitive blockadePersistant depolarization 2Non depolarizingDepolarizing 3Single blockDual block 4Anticholinesterases reverse blockade Do not reverse 5Initial fasciculations not present Present 6Slow onset long duration Rapid onset short duration 7Release histamineDoesn’t release

Dantrolene Directly acting skeletal Muscle relaxant Inhibits depolarization induced calcium release from sarcoplasmic reticulum by acting on ryanodine receptors Drug of choice in malignant hyperthermia

Drug interactions Non depolarizing blockers –Anticholine-esterases (Neostigmine) Reverse the action of only non depolarizing blockers –Halothane, Aminoglycoside antibiotic like gentamicin & calcium channel blockers like nifedipine Enhances the neuromuscular blockade Depolarizing blockers –Halothane can cause malignant hyperthermia

Ganglion blockers Competitive blockers –Hexamethonium –Trimethaphan –Mecamylamine Persistant depolarizing –Nicotine large dose

Actions & Adverse effects of ganglion blockers S.NoOrganDominant ANSEffect/(side effect)of ganglionic blockade 1.HeartParasympatheticTachycardia (Palpitations) 2.Blood vesselsSympatheticVasodilation (Hypotension) 3.IrisParasympatheticMydriasis (Photophobia) 4.Ciliary MuscleParasympatheticCycloplegia (Blurring of vision) 5.IntestinesParasympathetic↓ motility (Constipation) 6.BladderParasympathetic↓ tone (difficulty in micturation) 7.Male sexual functionParasympatheticInhibition of erection & ejaculation (Impotence) 8.Salivary GlandsParasympatheticInhibition of salivation (dry mouth, difficulty in swallowing) 9.Sweat GlandsSympatheticInhibition of sweating